Preparation method of azetidinone compounds and preparation method of 4-acyloxy azetidinone compounds
A technology of azetidinone and azetidinone, which is applied in the field of drug preparation and can solve the problems of poor selectivity and low yield
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
preparation example Construction
[0041] Among them, R 1 Selected from C 6 ~ C 20 Aryl or C 6 ~ C 20 Replantation aryl, C 5 ~ C 20 Fleet, C 3 ~ C 10 Any one or more of the cycloalkyl group, R 2 Selected from C 1 ~ C 10 Alkyl, C 2 ~ C 10 Alkenyl, C 2 ~ C 10 Alkynyl, C 2 ~ C 10 Ester, C 6 ~ C 20 Aryl and C 6 ~ C 20 Replantation aryl, C 5 ~ C 20 Fleet, C 3 ~ C 10 Any one or more of the cycloalkyl group, R 3 For silane, the preparation method comprises: step S1, the epoxyamide compound is carried out by a first alkali reagent to obtain a first reaction system, and a first reaction system comprises formula II, formula III, formula IV. Structure of compounds;
[0042]
[0043] Step S2, the first reaction system and the raw material including the silane element, the nitrogen-containing alkaline organic matter, to obtain a second reaction system, and the compound of the formula V and the formula I shown in the second reaction system. Structure of compounds;
[0044]
[0045] Step S3, the second reaction system is ...
Embodiment 1
[0078]
[0079] The first step, the ring reaction:
[0080] The epoxyamide compound 7 (50.0 g, 1.0 EQ) (50.0 g, 1.0 EQ) was dissolved in 150 mL of DMF, and potassium carbonate (7.87 g, 0.3 Eq) was added to 70 ° C. Reaction 12 h, HPLC monitors the peak area of the compound 7 2 SO 4 Dry, filtered, concentrated to remove the solvent to obtain a crude material 53.6 g, the compound 8 was measured from HPLC of 31.4 g, the yield was 62.7%, the compound 8a and 8b were a non-separable mixture, the mixture was 12.1 g, the mixture The rate was 24.1%, the total yield was 86.8%, which was directly used for the next reaction without purification.
[0081] The crude product was purified by column chromatography (the mixture could not be separated) for structural identification and HPLC standard preparation.
[0082] Nuclear magnetic data of Compound 8: 1 H NMR (500 MHz, CDCL 3 ) δ 7.18 (D, J = 8.9 Hz, 2H), 6.83 (D, J = 9.0 Hz, 2H), 4.56 (D, J = 2.6 Hz, 1H), 4.35-4.26 (M, 1H), 3.73 (S, 3H), 3...
Embodiment 2
[0092]
[0093] The first step, the ring reaction:
[0094] The epoxyamide compound 10 (50.0 g, 1.0 EQ) (50.0 g, 1.0 EQ) (50.0 g, 1.0 EQ) was dissolved in 150 mL of THF, and the solid superikrain HND63 was added (Jiangsu Nanta Synthetic Company purchased, 10 g , 0.2 g / g), warmed to 60 ° C for 2 h. After the HPLC monitors the peak area of the compound 10, the reaction system cools down, filtered, the filter cake was purified by 30 ml of THF, and the organic phase was combined, and the solvent was concentrated to obtain a crude product 11, and the content of the compound 11 was measured by HPLC. It was 34.1 g, the yield was 68.2%, the compounds 11a, and 11b were a non-separable mixture, and the mixture was 10.1 g, the yield of the mixture was 20.2%, the total yield was 88.4%, the crude product was directly used for step.
[0095] The crude product was purified by column chromatography (the mixture could not be separated) for structural identification and HPLC standard preparat...
PUM
Login to View More Abstract
Description
Claims
Application Information
Login to View More